As ionization methods for ionizing components in a sample which is the object of measurement in a mass analysis device, various methods have been proposed and put to practical use in the prior art. As an ionization method in which ionization is performed in an ambient pressure atmosphere, the electrospray ionization (ESI) method is well known, and one type of ionization method using this ESI that has gained attention in recent years is the probe electrospray ionization (PESI) method.
As disclosed in patent document 1, non-patent document 1, etc., the PESI ion source for performing ionization by the PESI method comprises a conductive probe with a probe diameter of about several hundred nanometers; a displacement unit which moves at least one of either the probe or the sample so as to cause the sample to adhere to the tip of the probe; and a high voltage generation unit which applies a high voltage to the probe in a state where sample has been collected on the tip of the probe. For example, during measurement, at least one of either the probe or the sample is moved by the displacement unit, causing the tip of the probe to contact or penetrate slightly into the sample, and causing a small quantity of sample to adhere to the probe tip surface. The probe is then moved away from the sample by the displacement unit, and a high voltage is applied to the probe from the high voltage generation unit. Thereupon, a strong electric field acts on the sample adhering to the probe tip, inducing an electrospray phenomenon whereby component molecules in the sample are eliminated and ionized.
Generally, ionization which utilizes the electrospray phenomenon has a higher ionization efficiency when compared to other ionization methods such as ionization methods based on irradiation with laser light. Thus, with a PESI ion source, molecules in a small quantity of sample can be efficiently ionized. Furthermore, it is possible, for example, to perform ionization on a very small quantity of biological tissue collected from a subject in its existing state, without performing any preprocessing, including dissolution or dispersion. Moreover, by changing the location on the sample into which the probe is inserted, ionization can be successively performed on multiple sites in a one-dimensional or two-dimensional region of the sample. This has the advantage of enabling distribution analysis of one-dimensional or two-dimensional regions.
Measurement using a mass analysis device utilizing a PESI ion source (hereinafter referred to as “PESI ionization mass analysis device”) is especially promising with respect to measurement of various components in living biological tissue. Namely, as described also in non-patent document 1, for example, a mouse in a living state under anesthesia is placed onto a sample platform in a supine position and laparotomized to expose biological tissue (for example, an organ), into which the probe is directly inserted to collect cells. The cells collected here are in a very small quantity and the insertion of the probe into the biological tissue is also very slight, so injury to the tissue can be kept to a minimum. By utilizing such measurement, it becomes possible to investigate the kinetics of various biochemical reaction cycles, including metabolic pathways, for example, to investigate the kinetics of the TCA (TriCarboxylic Acid) cycle, which is one metabolic pathway, by observing the change over time in acetyl CoA quantity in hepatic tissue after administering bilirubinic acid, which is produced in the glycolysis system, to experimental animals such as mice.